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High levels of short-chain fatty acids secreted by Candida albicans hyphae induce neutrophil chemotaxis via free fatty acid receptor 2
Department of Oral Microbiology and Immunology, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Medicinaregatan 12A, Gothenburg, Sweden.
Department of Oral Microbiology and Immunology, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Medicinaregatan 12A, Gothenburg, Sweden.
Department of Rheumatology and Inflammations Research, Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Guldhedsgatan 10A, Gothenburg, Sweden; Department of Life Sciences, Chalmers University of Technology, Kemigården 4, Gothenburg, Sweden.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
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2024 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 115, no 3, p. 536-546Article in journal (Refereed) Published
Abstract [en]

Candida albicans belongs to our commensal mucosal flora and in immune-competent individuals in the absence of epithelial damage, this fungus is well tolerated and controlled by our immune defense. However, C. albicans is an opportunistic microorganism that can cause different forms of infections, ranging from superficial to life-threatening systemic infections. C. albicans is polymorphic and switches between different phenotypes (e.g. from yeast form to hyphal form). C. albicans hyphae are invasive and can grow into tissues to eventually reach circulation. During fungal infections, neutrophils in particular play a critical role for the defense, but how neutrophils are directed toward the invasive forms of fungi is less well understood. We set out to investigate possible neutrophil chemoattractants released by C. albicans into culture supernatants. We found that cell-free culture supernatants from the hyphal form of C. albicans induced both neutrophil chemotaxis and concomitant intracellular calcium transients. Size separation and hydrophobic sorting of supernatants indicated small hydrophilic factors as responsible for the activity. Further analysis showed that the culture supernatants contained high levels of short-chain fatty acids with higher levels from hyphae as compared to yeast. Short-chain fatty acids are known neutrophil chemoattractants acting via the neutrophil free fatty acid receptor 2. In line with this, the calcium signaling in neutrophils induced by hyphae culture supernatants was blocked by a free fatty acid receptor 2 antagonist and potently increased in the presence of a positive allosteric modulator. Our data imply that short-chain fatty acids may act as a recruitment signal whereby neutrophils can detect C. albicans hyphae.

Place, publisher, year, edition, pages
Oxford University Press, 2024. Vol. 115, no 3, p. 536-546
Keywords [en]
acetate, GPR43, granulocyte, infection, inflammation
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-221856DOI: 10.1093/jleuko/qiad146ISI: 001168089900002PubMedID: 37992073Scopus ID: 2-s2.0-85186083719OAI: oai:DiVA.org:umu-221856DiVA, id: diva2:1843788
Funder
Swedish Research Council, 2019-01123Swedish Research Council, 2022-00561Available from: 2024-03-12 Created: 2024-03-12 Last updated: 2025-04-24Bibliographically approved

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Stylianou, MariosUrban, Constantin F.

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